This research will explore the regulation of ferritin phenotypes in mammalian cells. Using a combination of translational assays and cloned DNA hybridization techniques, shall investigate ferritin gene expression in normal and iron-loaded rat liver and Hela cells. cDNA to rat and human ferritin mRNAs will be cloned. These probes will be used to determine the number and distribution of ferritin mRNA species in free and membrane-bound polysomes and in messenger ribonucleoprotein (mRNP) particles. The structural relationships of ferritin mRNAs will be determined by sequencing. The number and chromosomal arrangement of ferritin genes will be examined to determine whether the different ferritin mRNAs arise from differential splicing of a common nuclear transcipt or from two or more genes. Factors regulating the rate of ferritin subunit synthesis will be explored, with particular attention to the role of ferritin mRNP particles in translational control. Developmental aspects of ferritin gene expression will be examined in Friend cells in collaborative studies. Finally, in other collaborative studies, we shall explore the possibility that abnormalities in ferritin gene expression are related to known abnormalties in iron metabolism.